Denosumab linked to severe hypocalcemia in dialysis-dependent seniors

For female dialysis-dependent patients aged 65 years or older treated for osteoporosis, denosumab is associated with an increased incidence of severe or very severe hypocalcemia, according to a study published online Jan. 19 in the Journal of the American Medical Association.

Steven T. Bird, Ph.D., Pharm.D., from the U.S. Food and Drug Administration in Silver Spring, Maryland, and colleagues examined the incidence and comparative risk for severe hypocalcemia with denosumab versus oral bisphosphonates in a retrospective cohort study involving female dialysis-dependent Medicare patients aged 65 years or older treated for osteoporosis. The main outcomes were severe hypocalcemia, defined as total albumin-corrected serum calcium <7.5 mg/dL or a primary hospital or emergency department hypocalcemia diagnosis, and very severe hypocalcemia (serum calcium <6.5 mg/dL).

Overall, 607 of 1,523 denosumab-treated patients and 23 of 1,281 oral bisphosphonate-treated patients developed severe hypocalcemia in the unweighted cohorts. The researchers found that the 12-week weighted cumulative incidence of severe hypocalcemia was 41.1 and 2.0% with denosumab and oral bisphosphonates, respectively (weighted risk ratio, 20.7). The 12-week weighted cumulative incidence of very severe hypocalcemia was 10.9 and 0.4% with denosumab and oral bisphosphonates, respectively (weighted risk ratio, 26.4).

"Given the complexity of diagnosing the underlying bone pathophysiology in dialysis-dependent patients, the high risk posed by denosumab in this population, and the complex strategies required to monitor and treat severe hypocalcemia, denosumab should be administered after careful patient selection and with plans for frequent monitoring," the authors write.